As much as 30% of oral cancers are reported to be related to an oncogenic HPV infection, and like other HPV- associated tumors, rates of oral cancer are highly elevated (6 to 8 fold) in HIV-infected patients relative to the general population. These rates have not decreased during the HAART era. Little is known, however, regarding oral precancer and non-dysplastic lesions, when the lesions are presumably easy to treat. Carcinogenesis, in particular HPV-associated carcinogenesis, is understood to be a multistage process. Therefore, determining the factors that predict progression from infection, low-grade disease to precancer and cancer is essential for identifying which of these lesions require treatment, as well as, to obtain insight into mechanisms that might be exploited to develop novel treatments. A first step in the process is a cross-sectional investigation comparing patients with no disease, low-grade dysplasia, and high-grade (precancerous) oral lesions, as a prelude to prospective cohort investigations that are extremely costly. We hypothesize that a higher fraction of oral dysplasias will be HPV-positive in HIV-infected versus HIV-uninfected patients, and that this fraction will increase incrementally with the degree of immunodeficiency (e.g., CD4+ T-cell counts or plasma HIV RNA levels). Specifically, in the current study, we will investigate the associations between oral HPV, lifestyle and immune-related factors in 200 HIV-infected patients through a cross-sectional evaluation of subjects without and with oral lesions that will be assessed for grade of dysplasia by histology, of which 40% may be dysplastic, if reports are correct. An additional sample of 100 HIV-uninfected patients without and with visible oral lesions will also be recruited. This project is being conducted within two urban, ethnic minority populations from NY (Bronx) and NJ (Newark). All subjects will be tested for oral HPV and HIV using standardized assays, and complete a comprehensive risk profile questionnaire. PUBLIC HEALTH RELEVANCE: Rates of oral cancer are highly elevated in HIV-infected individuals relative to the general population. The goal of this application is to investigate the associations between human papillomas virus, lifestyle and immune- related factors in an urban ethnic minority population of HIV-infected and uninfected patients with oral cancer precursor lesions.